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This one's of particular interest to me since my MS first presented as TM.

Key Protein Linked to Transverse Myelitis and Multiple Sclerosis

September 23, 2005 - Newswise — Hopkins researchers have discovered a single molecule that is a cause of an autoimmune disease in the central nervous system, called transverse myelitis (TM), that is related to multiple sclerosis.

In a study published in the October issue of The Journal of Clinical Investigation, psychiatrist Adam Kaplin, M.D., Ph.D., an assistant professor at The Johns Hopkins University School of Medicine, and neurologist Douglas Kerr, M.D., Ph.D., also an assistant professor at Hopkins, showed that the levels of the protein, IL-6, are dramatically elevated in the spinal fluid of transverse myelitis (TM) patients.

Although the majority of TM patients suffer a single attack, 15 percent to 30 percent of patients go on to develop full-blown MS. TM evolves rapidly and without warning and usually results in permanent impairment, including weakness of the legs and arms, bowel and bladder dysfunction, pain and paralysis.

IL-6 is a chemical messenger that cells of the immune system use to communicate with one another. One of the cell types injured by high levels of IL-6 includes oligodendrocytes, which help produce the protective myelin sheath coating around nerve cells. The findings offer one possible mechanism responsible for demyelinating disorders, such as TM and MS, and may aid in the development of effective therapies against these disorders, the researchers say.

“This is the first time a single culprit has been identified as causing a CNS autoimmune disease,” said Kaplin.

The researchers began investigating the protein IL-6 when they became aware that TM patients suffered from memory impairment and depression. IL-6 has been implicated in mood and concentration disorders.

“This discovery is a success story that begins with listening carefully to what patients are telling us about their suffering and then collaborating across disciplines to open up new avenues of investigation,” said Kaplin.

“TM is related to other autoimmune disorders of the nervous system, including Guillain-Barré syndrome, MS and acute disseminated encephalomyelitis. This study may give us a foothold in understanding all of these disorders and how they are linked together. The benefit is, therefore, not only to those who are paralyzed by TM, but to those who have disabilities due to a variety of autoimmune disorders. We are actively using these findings to aid in developing future diagnostic, prognostic and therapeutic advancements,” said Kerr, director of the Johns Hopkins Transverse Myelitis Center, the only center devoted to TM in the world.

Researchers analyzed 42 inflammatory proteins in the cerebrospinal fluid of both TM and healthy patients. They found that IL-6 was consistently elevated in TM patients’ spinal fluid. Further, the level of IL-6 directly correlated with the severity of paralysis.

Using cell culture and animal studies, the researchers confirmed that elevated IL-6 levels were directly injurious to the spinal cord. They showed that spinal fluid from TM patients induced death of spinal cord cells when cultured in a dish and that IL-6, when infused in adult rats, induced paralysis. Under the microscope, tissue from IL-6-infused rats showed demyelination and injury of axons, pathology that was nearly identical to that seen in human patients with TM.

Kerr and Kaplin also deduced that the reason IL-6 elevations injure only the spinal cord and not other regions of the nervous system was because distinct regions of the nervous system have different responses to IL-6. They concluded that these different types of responses might be a part of why different autoimmune disorders of the nervous system affect distinct regions and cause distinct symptoms.

“When we started, we knew nothing about the bad players in this drama in the spinal cord of CNS autoimmune diseases - it was a classic murder mystery and we set out together to find out ‘who done it’,” said Kaplin. “We’ve answered who could have done it, and how, and where.”

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I had to look into IL-6 a little more. There's a ton of information about it on Pubmed. There are a few experimental therapies for MS that seem to have an impact on IL-6. Ones I found in a quick search are:

In another laboratory study of human non-Hodgkin's lymphoma cells published in the September 2005 issue of Biochemical Pharmacology, University of Texas researchers showed that curcumin(TURMERIC) inhibits the activation of NF-kappaB, a regulatory molecule that signals genes to produce a slew of inflammatory molecules (including TNF, COX-2 and IL-6) that promote cancer cell growth. In addition, curcumin was found to suppress cancer cell proliferation and to induce cell cycle arrest and apoptosis (cell suicide) in the lung cancer cells. Early phase I clinical trials at the University of Texas are now also looking into curcumin's chemopreventive and therapeutic properties against multiple myeloma and pancreatic cancer, and other research groups are investigating curcumin's ability to prevent oral cancer.

According to Robert F. Grimble, Ph.D., of the University of Southampton, England, once an infection or injury stimulates production of IL-1 and TNFa, these two proinflammatory compounds can further stimulate each other, as well as IL-6. In addition, IL-1 and TNFa trigger the production of free radicals, which encourage the production of more proinflammatory cytokines. The proinflammatory reaction essentially feeds on itself, setting the stage for chronic inflammation. ,

Ideally, the body balances these compounds with a group of antiinflammatory compounds that originate with alpha-linolenic acid, found in cold-water fish, leafy green vegetables, and flaxseed. The body converts alpha-linolenic acid to the omega-3 family of fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Preformed EPA and DHA are also found in cold-water fish.

Much of the problem with inflammatory disorders actually stems from a lopsided imbalance in dietary intake of the omega-6 and omega-3 fatty acids-and the consequential cascade in proinflammatory activity. Artemis Simopolous, M.D., director of the Center for Genetics, Nutrition and Health in Washington, D.C., has shown that people historically consumed roughly equal amounts of the proinflammatory omega-6 fatty acids and the antiinflammatory omega-3 fatty acids.

However, over the past 30 years or so, Americans have replaced much of their dietary saturated fat (a bystander, so far as inflammation is concerned) with omega-6 fatty acids. Simopoulos estimates that people are now eating 20 times more omega-6s than omega-3s. From a biochemical standpoint, this sets the stage for powerful and chronic proinflammatory reactions.
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Once again hubby has shown dramatic improvement since June of this year after starting on Turmeric as well as Cold water fish 5-7 times per week starting slowly in Feb 2005 to out current level in April. The inflammation IMO is the major problem. Handle the inflammation and restore your system through elimination of toxins, allergens as well as intolerances. Some toxins include aspartame,caffeine,processed foods,lunch meats and number 1 smoking. These are opinions but I have no doubt the path we have chosen to follow has improved our life. We will continue to eat healthy as well as exercise and to keep out as many toxins as possible. Hubby is also on Lipitor 40 mg as well as vitamin D3 and started Copaxone on July 4 2005.

I don't know anything about it but here are some links that might help us to understand

Interleukin-6

Interleukin-6 (IL-6) is a variably glycosylated, secreted 22-27 kDa glycoprotein with a helical structure. It is a pro-inflammatory cytokine that is present at low levels in the plasma of normal individuals, but which shows substantial increases in response to a number of pathological conditions including cancer and acute coronary syndromes. It is a primary mediator of the acute phase response, with levels greatly increased after surgery.

IL-6 is an independent predictor of mortality, cardiovascular events and development of type 2 diabetes in healthy individuals and of mortality in those with coronary heart disease. Among apparently healthy men, individuals with IL-6 values in the highest quartile (IL-6 > 2.28 pg/mL) were 2.3 times more likely to suffer a myocardial infarction than individuals in the lowest quartile (IL-6 < 1.04 pg/mL; Circulation 2000;101:1767-1772).

Assays for human IL-6 are widely available. However, routine measurement of IL-6 is not currently recommended for assessment of risk in any population.

Levels of IL-6 can be reduced by weight reduction and by 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Angiotensin receptor blockers, oral antihyperglycaemic agents and cyclo-oxygenase-2 inhibitors have also been shown to reduce IL-6 levels.

Intro, Summary & Key Details

Background Information

Clinical Trials Data

Clinical Practice and Procedure

Which patients to measure?

Prospective treatments

Interleukin-6 (IL-6) is a pro-inflammatory cytokine and a major mediator of the acute phase response. It has a range of humoral and cellular immune effects that play a central role in host defence, tissue injury and inflammation. It may also have procoagulant properties.

IL-6 is released by a range of tissues, such as muscle, in response to stimulation by the monocyte-derived cytokines interleukin-1 (IL-1) and tumour necrosis factor. It is expressed by macrophage foam cells and smooth muscle cells in fatty streaks and in the 'cap' and 'shoulder' regions of atheromatous plaques. By reflecting the intensity of plaque inflammation, plasma levels of IL-6 may be an indicator of the vulnerability of plaque rupture. In this way, IL-6 may play a direct role in the progression of atherosclerosis.

IL-6 may also have indirect effects on the progression of cardiovascular disease. It is the primary driver for hepatic synthesis of C-reactive protein (CRP), the well-validated independent risk marker for atherosclerotic disease. Despite of the close relationship between IL-6 and CRP, several studies have found that the value of IL-6 as a predictor of cardiovascular events is independent of CRP.

Adipose tissue is a potent source of IL-6, which may play a role in the association between obesity and cardiovascular disease. IL-6 is also an independent risk marker for type 2 diabetes.

Sensitive and specific commercial IL-6 assays are available for use with serum, plasma and urine. In healthy individuals, plasma IL-6 levels are usually 1 pg/mL. IL-6 plays a central role in inflammation, tissue injury and defence against infection. Its levels are increased in a number of pathological conditions, and by strenuous exercise. Elevated IL-6 levels are thus not specific for cardiovascular or metabolic disease.

Interleukin-6 has a shorter half-life (4 hours) than other markers of inflammation, such as CRP and serum amyloid A (19 hours). IL-6 levels also show diurnal variation. These features may limit the clinical utility of IL-6 as an inflammatory risk marker. The use of indwelling intravenous catheters for repeated assay of plasma IL-6 levels should be undertaken with caution (Psychoneuroendocrinology 2002;27:921-31).

A numeric relationship between IL-6 level and generalised cardiovascular risk or mortality has not been established. However, a study of apparently healthy men found those with IL-6 values in the highest quartile (IL-6 > 2.28 pg/mL) were 2.3 times more likely to suffer a myocardial infarction than those in the lowest quartile (IL-6 < 1.04 pg/mL; Circulation 2000;101:1767-1772).

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Measurement of IL-6 is not currently recommended in routine risk assessments. However, IL-6 is an independent risk marker of mortality, cardiovascular events and type 2 diabetes in healthy individuals, as well as mortality in those with coronary heart disease. The value of IL-6 as an independent predictor of cardiovascular events is retained even in low-risk subgroups, such as non-smoking men.

These data suggest that routine screening for IL-6 might be beneficial in identifying individuals at increased risk of diabetes and atherosclerotic events, particularly in those not identified using traditional risk factors. However, as levels of IL-6 and CRP are linked, and as CRP is generally the stronger predictor of cardiovascular events than IL-6, of the two, CRP is maybe the more useful inflammatory risk marker.

I had intended to add this a while ago and lost track of my pile of articles on IL-6. This is also work by Kaplin that precedes the noted article from newswise. But in this case you can get the entire Journal article. It is interesting to wonder if this is somehow the cause of MS.

All of these reports are just fascinating to me. If the IL-6 is the possible culprit in causing MS, I can see where my own lifestyle would have been a factor in developing this disease.

Prior to my 30's I almost never ate fish or other foods containing ALA, such as flaxseeds. Apparently these foods keep the IL-6's down in our body and inflammation is contained.

Other foods which used to contain high levels of omega 3's are beef and other grass eating animals. For decades though, we have feed these animals less grass and more nutritionally deficit corn and grains and less omega 3 grass.

Since I am allergic to all red meats, I eat a lot of pork, which is from an animal that relishes slop and other crummy foodstuffs with little food value for them.

Eskimos, who eat buckets of high Omega-3 salmon, do not get MS. The salmon eat plants which contain the ALA oils.

It appears to me that a low calorie diet coupled with eating a lot of salmon and flaxseed muffins would lower the IL-6 to an axonal protective level.

For the past decade I have eaten lots of salmon, flaxseed muffins and green salads. During this time I have been relatively stable, though still slowly worsening, so maybe this diet is somewhat helpful.

There is so much information posted here about the IL-6 connection to MS that it is hard to digest it all.

gwa

Last edited by gwa on Sat Dec 30, 2006 9:48 am, edited 1 time in total.

This is hugely interesting. I'm going to look further but I happened to be on NYTIMES website and searched IL-6 and came up with a health article on DHEA indicating that when the hormone is given to older men and women it produced lower levels of interleukin-6 (along with higher levels of infection-fighting natural killer cells). This may be one of the ways that, DHEA appears to provide neuroprotection.

Now, that study goes on to say it didn't change the clinical outcome in EAE mice at certain doses, but subsequent EAE studies found DHEA did have an impact. There were also two positive Phase I Clinical trials of DHEA and DHEA levels seem to be consistently low in people with MS.

Mean DHEAS levels were lower in MS patients compared with healthy controls (P = 0.049), but there were no significant differences between the clinical subgroups of MS.

I think DHEA does impact natural killer cells too but I don't have that info at hand.

Just so you know - IL-6 is secreted in response to infection and other trauma as described by wikepedia; "Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. In terms of host response to a foreign pathogen, IL-6 has been shown, in mice, to be required for resistance against the bacterium, Streptococcus pneumoniae[1]. IL-6 is also a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction[2]. Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation."

This is really interesting. Serum uric acid and IL-6 have also been studied in relation to cardiovascular disease...but having a brain fog day after eating pure rubbish for all of Xmas and deviating from my diet...........cannot pull the logic together.............can anyone help?

Also, if Omega-6's are capable of raising IL-6, then why are some of us taking evening primrose oil? Surely that would be one to avoid if it raises IL6...?

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